TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart failure

Abstract

Doxorubicin (Dox) is limited in its use because of its adverse effect of inducing irreversible heart dysfunction. Innate immune factors, including toll-like receptors (TLRs), play important roles in most cardiac diseases and doxorubicin-induced cardiotoxicity. In this study, subjects were divided into the following groups: healthy controls (n = 62), HF group (n = 60), Dox group (n = 82), and Dox-HF group (n = 32). Expressions of TLR mRNAs in peripheral blood mononuclear cells were detected by RT-PCR. Western blotting was used to quantify protein expressions of Peripheral blood mononuclear cells (PBMCs) TLRs and their downstream signal proteins. The release of inflammatory factors was detected by ELISA. Results indicated that TLR2 was increased and TLR3 was decreased between the control group and Dox group, and between the Dox group and Dox-HF group. Serum inflammatory factors were comparable between the HF group, the Dox group, and the Dox-HF group. This study suggested that TLR2 and TLR3 are up- and down-regulated, respectively, in doxorubicin-treated patients who develop heart dysfunctions. This may suggest a predictive role for TLR2-TLR3 imbalance in doxorubicin-induced heart failure.